Prostate cancer is the most common non-skin malignancy in men, second only to lung cancer for cancer-related male deaths in the United States. There is a high prevalence of latent or occult prostate cancer in U.S. males over 50 years old. That is, post mortem studies have estimated that approximately 30 percent of males older than age 50 have histologic evidence of prostate cancer, in which it is even reported that some U.S. males, as early as 20 years of age, have detectable precursor lesions. Therefore, it is not surprising that the presence of microscopic adenocarcinoma foci in 30 to 50 year old U.S. males has been estimated to range from 25 to 32 percent. Yet, prostate cancer is relatively uncommon in male populations in many Asian countries.
Epidemiological studies have suggested that dietary intake of fruits and vegetables and other plant-related products may provide significant chemopreventive effects against hormone-related cancers. A number of micronutrients, in particular, β-carotene, ascorbic acid, α-tocopherol and folic acid, have been intensely studied to elucidate any corresponding chemopreventive effects that these micronutrients may convey when consumed. However, many of the results of these micronutrient studies have led to contradictory or inconclusive findings concerning their chemopreventive effectiveness.
A growing body of evidence indicates that anutrients, hereinafter defined as non-nutrient phytochemicals, such as anti-oxidants, dithiothriones, phenols, indoles, flavonoids, protease inhibitors and allium compounds, may also play key roles in either blocking or suppressing carcinogenic processes. Even though it is now generally considered that a wide variety of anutrients in plant-related diets is a primary contributor to chemoprevention, it is generally believed that a single anutrient compound is unlikely to be the sole cause of chemoprevention from these plant-related diets. Rather it appears that it is likely that multiple anutrient components impinge on multiple key cell growth signaling pathways simultaneously as the primary prevention mechanism of any cancer attributable to anutrients.
More recently, a subcategory of phytochemical anutrients, i.e., the secondary products of plant mevalonate metabolism, collectively defined herein as isoprenoids, has been recognized for its potential use in cancer prevention and treatment possibilities. Isoprenoid anutrient compounds are derived entirely or in part from the plant mevalonate biosynthetic pathway, which are further subcategorized into “pure” or “mixed” isoprenoids. Pure isoprenoids have varying structures consisting only of five-carbon isoprene units, e.g., monoterpenes, diterprenes, etc. Some important examples of pure isoprenoids include farnesol, limonene, perillyl alcohol, lycopenes, β-carotenes and ionone. Mixed isoprenoids include isoflavones, prenylated coumarins, flavones, flavanols, chalcones, quinones, and chromanols, each with only a part of the molecule derived via the mevalonate pathway. Some important examples of mixed isoprenoids include the tocotrienols.
Therefore, it is not surprising that a large number of studies have established the anti-tumorigenic properties of pure isoprenoids. It has been clearly shown that isoprenoids, e.g., limonene, perillyl alcohol, γ-tocotrienol, β-ionone, and farnesol, initiate apoptosis and concomitantly arrest cancer cells in the G1 phase of the cell cycle. Tocotrienols have been shown to be especially effective at inhibiting growth of both murine and human breast cancer cells in culture. Pure and mixed isoprenoids have been shown to suppress growth of a vast number of whole animal tumor models including implanted leukemic cells, melanomas, pancreatic tumors and hepatomas.
Since many forms of cancer are considered incurable, in particular prostate cancer, then treatment methods and associated compounds aimed at impeding growth of cancer cell growth are likely to be found useful in aiding in the cure and prevention of these cancers. Therefore, there is a need to identify new and useful compounds and associated methods to treat various cancers for use in impeding cancer cell growth.